Program Director/Principal Investigator (Last, First, Middle): Anderson, Cheryl, A. M. Revised abstract: The overall objective of this study is to examine the effects of dietary sodium intake on sodium regulation in adults enrolled in a randomized controlled trial (RCT) recently funded by the Alliance for Potato Research and Education (https://apre.org) -- a non-profit organization funded by the potato industry [PI: Connie Weaver, PhD at Purdue University). The rationale for this work is the strong evidence that dietary sodium has a strong, direct, and progressive relationship with blood pressure, and is causally implicated in hypertension, and subclinical and clinical cardiovascular disease (CVD). There is also considerable interest in the associations of dietary sodium with CVD that are independent of the association with blood pressure. To advance clinical practice and strengthen the evidence supporting public health guidelines, studies are needed to elucidate the mechanisms by which different levels of dietary sodium intake influence sodium regulation. This proposal is timely and relevant as emerging data challenge the dogma that sodium balance is regulated solely by the kidneys and urinary sodium excretion is roughly equivalent to sodium consumed on a day-to-day basis. Our prior work showed racial disparities in sodium retention (i.e., intake minus excretion) in youth consuming the same high sodium diets such that blacks retained much more sodium than whites, but without effects on weight or blood pressure. This finding led us to hypothesize that sodium may be accumulating in the bones of youth, who are black, while rapid growth is occurring. Recently published data in adults suggest there are regulatory sodium clearance mechanisms in soft tissues (i.e., skin and muscle), and that urinary sodium excretion fluctuates in a week-long pattern depending on hormones. An important limitation of the existing body of research related to this proposal is that very few studies have had the capacity to utilize the newest techniques for measuring sodium distribution in soft issues and bone when dietary sodium intake is known. The few studies in this area are mostly in animals. The proposed study fills an important gap as it uses a randomized clinical trial design, with feeding of a controlled diet. We will measure outcomes in blood, urine, muscle, skin, and bone. This will further the science examining whether sodium retention leads to sodium deposits in bone or soft tissues without commensurate water accumulation, a process which likely influences risk of hypertension. In summary, we propose to leverage the infrastructure of an already funded feeding study to examine sodium regulation in adults consuming known amounts of dietary sodium and potassium. The funded trial is focused on examining the difference in potassium retention between potato sources and supplements, and how this affects cardiometabolic outcomes and mineral metabolism. Measurements from urine, skin, muscle, bone, and hormones will be conducted. SPECIFICALLY, WE AIM TO: 1(a): Determine the effects of high and low dietary sodium intake on stores of sodium (i.e., skin, muscle and bone) and on urea production. 1(b): Determine whether sodium distribution mediates the relationship between dietary sodium and blood pressure. Hypotheses: a) Isolated measurement of 24-hour urinary sodium is an inadequate marker of short-term sodium intake, and is an incomplete explanation for the relationship of sodium to blood pressure. Additionally, high sodium intake changes energy metabolism such that urea production and energy expenditure increases; b) Measurements of skin, muscle, and bone are needed to represent sodium distribution and elucidate effects on blood pressure. 2: Determine the effects of high and low sodium intake on urinary sodium excretion and urinary potassium excretion; and whether these effects are modified by hormone regulators (aldosterone, free cortisol, free cortisone, ratio of free cortisone to free cortisol, glucocorticoid, and mineralocorticoid). Hypothesis: Urinary hormone levels will correlate with changes in urinary sodium and potassium excretion; and will vary by high and low sodium intake. Secondary Aim: To examine and report differences by important clinical and demographic factors in sodium regulation and potassium excretion (Aims 1a, 1b, and 2).